Abstract. Thirty-five cases of renal medullary crest necrosis morphologically similar to the renal papillary necrosis of analgesic nephropathy as described in man and rats are reported in horses receiving maintenance dosages of phenylbutazone. The primary lesion is a well-demarcated focal medullary necrosis resulting in sequestration of fragments of the renal crest. Renal cortical lesions are considered secondary to the medullary necrosis and consist of segmental pallor as a result of tubular dilatation, filtrate retention, and interstitial edema. Ischemia in concert with phenylbutazone is suggested as the etiology. Renal medullary crest necrosis is presented as more appropriate morphological terminology for this lesion in the equine species than renal papillary necrosis as is used in man and rats.The nephrotoxicity of non-steroidal anti-inflammatory drugs in man is well known [8,12, 191. The drugs most commonly implicated in analgesic nephropathy are aspirin, phenacetin, and caffeine [ 121, although the phenylalkalonic acids fenoprofen, naproxen, and phenylbutazone also are incriminated [6, 1 1, 12, 181. A characteristic lesion of analgesic nephropathy is renal papillary necrosis [8,12, 191, and this lesion has been produced experimentally in rats with phenylbutazone and indomethacin [ I , 21 and in rats and rabbits with phenacetin and salicylates [ 3 , 101 and demonstrated to be the result of medullary ischemia [9, 131. Phenylbutazone is the most popular and widely used non-steroidal anti-inflammatory agent in equine medicine [4,7, 16, 171; however, morphological lesions associated with phenylbutazone toxicity in horses have been reported only rarely [5. 14, 151. Experimentally induced phenylbutazone toxicity in ponies has resulted in oral, gastric, duodenal, cecal, and colonic ulcers [ 14, 151. In an unrelated study in Thoroughbred and Standardbred horses, phenylbutazone produced oral and gastric ulcers in two horses [ 5 ] . Necrotizing phlebitis of the portal vein also was attributed to phenylbutazone toxicity [5].Although renal lesions commonly are ascribed to analgesic toxicities in man [8, 121 and rats [ l , 2, lo], no morphological lesions associated with the clinical use of phenylbutazone have been described in the kidneys of horses. The purpose of this paper is to report the spontaneous occurrence in 35 horses of renal medullary crest 662